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nmdar inhibition

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https://www.readbyqxmd.com/read/28634445/antioxidant-treatment-with-n-acetyl-cysteine-prevents-the-development-of-cognitive-and-social-behavioral-deficits-that-result-from-perinatal-ketamine-treatment
#1
Aarron Phensy, Hasmik E Duzdabanian, Samantha Brewer, Anurag Panjabi, Christopher Driskill, Annuska Berz, George Peng, Sven Kroener
Alterations of the normal redox state can be found in all stages of schizophrenia, suggesting a key role for oxidative stress in the etiology and maintenance of the disease. Pharmacological blockade of N-methyl-D-aspartic acid (NMDA) receptors can disrupt natural antioxidant defense systems and induce schizophrenia-like behaviors in animals and healthy human subjects. Perinatal administration of the NMDA receptor (NMDAR) antagonist ketamine produces persistent behavioral deficits in adult mice which mimic a range of positive, negative, and cognitive symptoms that characterize schizophrenia...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/28630250/amplification-of-mglu5-endocannabinoid-signaling-rescues-behavioral-and-synaptic-deficits-in-a-mouse-model-of-adolescent-and-adult-dietary-polyunsaturated-fatty-acids-imbalance
#2
Antonia Manduca, Anissa Bara, Thomas Larrieu, Olivier Lassalle, Corinne Joffre, Sophie Layé, Olivier J Manzoni
Energy-dense, yet nutritionally-poor food is a high-risk factor for mental health disorders. This is of particular concern during adolescence, a period often associated with increased consumption of low nutritional content food and higher prevalence of mental health disorders. Indeed, there is an urgent need to understand the mechanisms linking unhealthy diet and mental disorders. Deficiency in n-3 polyunsaturated fatty acid (PUFAs) is a hallmark of poor nutrition and mood disorders. Here, we developed a mouse model of n-3 PUFAs deficiency lasting from adolescence into adulthood...
June 19, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28620235/a-non-ionotropic-activity-of-nmda-receptors-contributes-to-glycine-induced-neuroprotection-in-cerebral-ischemia-reperfusion-injury
#3
Juan Chen, Rong Hu, Huabao Liao, Ya Zhang, Ruixue Lei, Zhifeng Zhang, Yang Zhuang, Yu Wan, Ping Jin, Hua Feng, Qi Wan
NMDA receptor (NMDAR) is known for its ionotropic function. But recent evidence suggests that NMDAR also has a non-ionotropic property. To determine the role of non-ionotropic activity of NMDARs in clinical relevant conditions, we tested the effect of glycine, a co-agonist of NMDARs, in rat middle cerebral artery occlusion (MCAO), an animal model of cerebral ischemia-reperfusion injury after the animals were injected with the NMDAR channel blocker MK-801 and the glycine receptor antagonist strychnine. We show that glycine reduces the infarct volume in the brain of ischemic stroke animals pre-injected with MK-801 and strychnine...
June 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28608233/alleviation-by-gabab-receptors-of-neurotoxicity-mediated-by-mitochondrial-permeability-transition-pore-in-cultured-murine-cortical-neurons-exposed-to-n-methyl-d-aspartate
#4
Toshihiko Kinjo, Yoshino Ashida, Hiroshi Higashi, Satoshi Sugimura, Miho Washida, Hiroki Niihara, Kiyokazu Ogita, Yukio Yoneda, Nobuyuki Kuramoto
Mitochondrial permeability transition pore (PTP) is supposed to at least in part participate in molecular mechanisms underlying the neurotoxicity seen after overactivation of N-methyl-D-aspartate (NMDA) receptor (NMDAR) in neurons. In this study, we have evaluated whether activation of GABAB receptor (GABABR), which is linked to membrane G protein-coupled inwardly-rectifying K(+) ion channels (GIRKs), leads to protection of the NMDA-induced neurotoxicity in a manner relevant to mitochondrial membrane depolarization in cultured embryonic mouse cortical neurons...
June 12, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28596523/extrasynaptic-nmda-receptor-dependent-long-term-potentiation-of-hippocampal-ca1-pyramidal-neurons
#5
Qian Yang, Geng Zhu, Dandan Liu, Jue-Gang Ju, Zhen-Hua Liao, Yi-Xin Xiao, Yue Zhang, Naijian Chao, JieJie Wang, Weidong Li, Jian-Hong Luo, Sheng-Tian Li
In the adult mouse hippocampus, NMDA receptors (NMDARs) of CA1 neurons play an important role in the synaptic plasticity. The location of NMDARs can determine their roles in the induction of long-term potentiation (LTP). However, the extrasynaptic NMDARs (ES-NMDARs) dependent LTP haven't been reported. Here, through the use of a 5-Hz stimulation and MK-801 (an irreversible antagonist of NMDARs) in the CA1 neurons of adult mice hippocampal slices, synaptic NMDARs were selectively inhibited and NMDAR-mediated excitatory postsynaptic currents were not recovered...
June 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28595035/n-methyl-d-aspartate-receptors-mediate-epilepsy-induced-axonal-impairment-and-tau-phosphorylation-via-activating-glycogen-synthase-kinase-3%C3%AE-and-cyclin-dependent-kinase-5
#6
Xi Liu, Shu Ou, Maojia Yin, Tao Xu, Teng Wang, Ying Liu, Xueying Ding, Xinyuan Yu, Jinxian Yuan, Hao Huang, Xiuhang Zhang, Xinjie Tan, Lifen Chen, Yangmei Chen
The mechanism of epilepsy-induced axonal impairment is poorly understood. N-methyl-D-aspartate receptors (NMDARs) play important roles in epilepsy and mediate structural and functional axonal impairment. GSK-3β and Cdk5 affect axons and are regulated by NMDARs, while their roles in epilepsy-induced axonal impairment are unclear. We demonstrated that axonal impairment is characterized by neurofilament heavy (NFH) reduction, amyloid precursor protein (APP) accumulation, and increased tau phosphorylation accompanied by a decrease of total tau in temporal lobe epilepsy (TLE) patients and pentylenetetrazol (PTZ)-kindled rats...
April 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28550530/rtms-ameliorates-ptsd-symptoms-in-rats-by-enhancing-glutamate-transmission-and-synaptic-plasticity-in-the-acc-via-the-pten-akt-signalling-pathway
#7
Gaohua Liu, Dayun Feng, Jian Wang, Haifeng Zhang, Zhengwu Peng, Min Cai, Jing Yang, Ruiguo Zhang, Huaning Wang, Shengxi Wu, Qingrong Tan
Repetitive transcranial magnetic stimulation (rTMS) is a novel physiological therapy that has been adopted to clinically treat psychiatric disorders. Our previous study indicated the potential therapeutic effect of rTMS on posttraumatic stress disorder (PTSD). However, the exact molecular mechanism is elusive. Currently, using the single prolonged stress (SPS) rat model for PTSD, we investigated the glutamatergic transmission and neural plasticity changes in the anterior cingulate cortex (ACC) after SPS induction and explored the protective effects and mechanism of rTMS treatment...
May 26, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28543279/role-of-ampa-receptors-in-homocysteine-nmdar-induced-crosstalk-between-erk-and-p38-map-kinase
#8
Ranjana Poddar, Alexandria Chen, Lucas Winter, Sathyanarayanan Rajagopal, Surojit Paul
Homocysteine, a metabolite of the methionine cycle has been reported to play a role in neurotoxicity through activation of NMDAR-mediated signaling pathway. The proposed mechanisms associated with homocysteine-NMDAR induced neurotoxicity involve a unique signaling pathway that triggers a crosstalk between ERK and p38 MAPKs, where activation of p38 MAPK is downstream of and dependent on ERK MAPK. However, the molecular basis of the ERK MAPK mediated p38 MAPK activation is not understood. The current study investigates whether AMPARs play a role in facilitating the ERK MAPK mediated p38 MAPK activation...
May 24, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28536523/positive-modulatory-interactions-of-nmda-receptor-glun1-2b-ligand-binding-domains-attenuate-antagonists-activity
#9
Douglas Bledsoe, Ceyhun Tamer, Ivana Mesic, Christian Madry, Bradley G Klein, Bodo Laube, Blaise M Costa
N-methyl D-aspartate receptors (NMDAR) play crucial role in normal brain function and pathogenesis of neurodegenerative and psychiatric disorders. Functional tetra-heteromeric NMDAR contains two obligatory GluN1 subunits and two identical or different non-GluN1 subunits that include six different gene products; four GluN2 (A-D) and two GluN3 (A-B) subunits. The heterogeneity of subunit combination facilities the distinct function of NMDARs. All GluN subunits contain an extracellular N-terminal Domain (NTD) and ligand binding domain (LBD), transmembrane domain (TMD) and an intracellular C-terminal domain (CTD)...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28533113/a-novel-serine-racemase-inhibitor-suppresses-neuronal-over-activation-in-vivo
#10
Hisashi Mori, Ryogo Wada, Satoyuki Takahara, Yoshikazu Horino, Hironori Izumi, Tetsuya Ishimoto, Tomoyuki Yoshida, Mineyuki Mizuguchi, Takayuki Obita, Hiroaki Gouda, Shuichi Hirono, Naoki Toyooka
Serine racemase (SRR) is an enzyme that produces d-serine from l-serine. d-Serine acts as an endogenous coagonist of NMDA-type glutamate receptors (NMDARs), which regulate many physiological functions. Over-activation of NMDARs induces excitotoxicity, which is observed in many neurodegenerative disorders and epilepsy states. In our previous works on the generation of SRR gene knockout (Srr-KO) mice and its protective effects against NMDA- and Aβ peptide-induced neurodegeneration, we hypothesized that the regulation of NMDARs' over-activation by inhibition of SRR activity is one such therapeutic strategy to combat these disease states...
May 11, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28513836/facilitation-of-mossy-fibre-driven-spiking-in-the-cerebellar-nuclei-by-the-synchrony-of-inhibition
#11
Yeechan Wu, Indira M Raman
Large projection neurons of the cerebellar nuclei (CbN cells), whose activity generates movement, are inhibited by Purkinje cells and excited by mossy fibres. The high convergence, firing rates, and strength of Purkinje inputs predict powerful suppression of CbN cell spiking, raising the question of what activity patterns favor excitation over inhibition. Recording from CbN cells at near-physiological temperatures in cerebellar slices from weanling mice, we measured the amplitude, kinetics, voltage-dependence, and short-term plasticity of mossy fibre-mediated EPSCs...
May 17, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28497801/pde4-inhibition-restores-the-balance-between-excitation-and-inhibition-in-vta-dopamine-neurons-disrupted-by-repeated-in-vivo-cocaine-exposure
#12
Xiaojie Liu, Peng Zhong, Casey Vickstrom, Yan Li, Qing-Song Liu
Phosphodiesterase type 4 (PDE4) is a family of enzymes that selectively degrade intracellular cAMP. PDE4 inhibitors have been shown to regulate the rewarding and reinforcing effects of cocaine, but the underlying mechanisms remain poorly understood. Here we show that pretreatments with the PDE4 inhibitor rolipram attenuated cocaine-induced locomotor sensitization in mice. Repeated cocaine exposure in vivo caused a decrease in inhibitory postsynaptic currents (IPSCs) and an increase in the AMPAR/NMDAR ratio in ventral tegmental area (VTA) dopamine neurons in midbrain slices ex vivo...
May 12, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28486599/antenatal-blockade-of-nmda-receptors-by-memantine-reduces-the-susceptibility-to-diabetes-induced-by-a-high-fat-diet-in-rats-with-intrauterine-growth-restriction
#13
Xiao-Ting Huang, Shao-Jie Yue, Chen Li, Jia Guo, Yan-Hong Huang, Jian-Zhong Han, Dan-Dan Feng, Zi-Qiang Luo
Intrauterine growth retardation (IUGR) is closely related to the later development of type 2 diabetes in adulthood. Excessive activation of glutamate receptors causes excitatory neurotoxicity, which is primarily mediated by N-methyl-D-aspartate receptors (NMDARs), resulting in neuronal injury or death. Inhibition of NMDARs enhances the GSIS and survival of islet cells in type 2 diabetic mouse and human islets. Here, we examined whether antenatal blockade of NMDARs by Memantine could decrease the risk of diabetes induced by a high-fat (HF) diet at adulthood in IUGR rats...
May 8, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28452419/neurosteroid-sensitive-%C3%AE-gabaa-receptors-a-role-in-epileptogenesis
#14
Suchitra Joshi, Karthik Rajasekaran, John Williamson, Jaideep Kapur
OBJECTIVE: We determined the role of the neurosteroid-sensitive δ subunit-containing γ-aminobutyric acid A receptors (δ-GABARs) in epileptogenesis. METHODS: Status epilepticus (SE) was induced via lithium pilocarpine in adult rats, and seizures were assessed by continuous video-electroencephalography (EEG) monitoring. Finasteride was administered to inhibit neurosteroid synthesis. The total and surface protein expression of hippocampal δ, α4, and γ2 GABAR subunits was studied using biotinylation assays and Western blotting...
March 2017: Epilepsia
https://www.readbyqxmd.com/read/28442607/n-methyl-d-aspartate-nmda-receptor-blockade-prevents-neuronal-death-induced-by-zika-virus-infection
#15
Vivian V Costa, Juliana L Del Sarto, Rebeca F Rocha, Flavia R Silva, Juliana G Doria, Isabella G Olmo, Rafael E Marques, Celso M Queiroz-Junior, Giselle Foureaux, Julia Maria S Araújo, Allysson Cramer, Ana Luíza C V Real, Lucas S Ribeiro, Silvia I Sardi, Anderson J Ferreira, Fabiana S Machado, Antônio C de Oliveira, Antônio L Teixeira, Helder I Nakaya, Danielle G Souza, Fabiola M Ribeiro, Mauro M Teixeira
Zika virus (ZIKV) infection is a global health emergency that causes significant neurodegeneration. Neurodegenerative processes may be exacerbated by N-methyl-d-aspartate receptor (NMDAR)-dependent neuronal excitoxicity. Here, we have exploited the hypothesis that ZIKV-induced neurodegeneration can be rescued by blocking NMDA overstimulation with memantine. Our results show that ZIKV actively replicates in primary neurons and that virus replication is directly associated with massive neuronal cell death. Interestingly, treatment with memantine or other NMDAR blockers, including dizocilpine (MK-801), agmatine sulfate, or ifenprodil, prevents neuronal death without interfering with the ability of ZIKV to replicate in these cells...
April 25, 2017: MBio
https://www.readbyqxmd.com/read/28439098/uncoupling-dapk1-from-nmda-receptor-glun2b-subunit-exerts-rapid-antidepressant-like-effects
#16
S-X Li, Y Han, L-Z Xu, K Yuan, R-X Zhang, C-Y Sun, D-F Xu, M Yuan, J-H Deng, S-Q Meng, X-J Gao, Q Wen, L-J Liu, W-L Zhu, Y-X Xue, M Zhao, J Shi, L Lu
Several preclinical studies have reported the rapid antidepressant effects of N-methyl-D-aspartate receptor (NMDAR) antagonists, although the underlying mechanisms are still unclear. Death-associated protein kinase 1 (DAPK1) couples GluN2B subunits at extrasynaptic sites to regulate NMDAR channel conductance. In the present study, we found that chronic unpredictable stress (CUS) induced extracellular glutamate accumulation, accompanied by an increase in the DAPK1-NMDAR interaction, the high expression of DAPK1 and phosphorylated GluN2B at Ser1303, a decrease in phosphorylated DAPK1 at Ser308 and synaptic protein deficits in the rat medial prefrontal cortex (mPFC)...
April 25, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28432142/structural-similarities-between-neuregulin-1-3-isoforms-determine-their-subcellular-distribution-and-signaling-mode-in-central-neurons
#17
Detlef Vullhorst, Tanveer Ahmad, Irina Karavanova, Carolyn Keating, Andres Buonanno
The Neuregulin (NRG) family of ErbB ligands is comprised of numerous variants originating from the use of different genes, alternative promoters, and splice variants. NRGs have generally been thought to be transported to axons and presynaptic terminals where they signal via ErbB3/4 receptors in paracrine or juxtacrine mode. However, we recently demonstrated that unprocessed pro-NRG2 accumulates on cell bodies and proximal dendrites, and that NMDAR activity is required for shedding of its ectodomain by metalloproteinases...
May 24, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28404816/the-pick1-ca-2-sensor-modulates-n-methyl-d-aspartate-nmda-receptor-dependent-microrna-mediated-translational-repression-in-neurons
#18
Dipen Rajgor, Maria Fiuza, Gabrielle T Parkinson, Jonathan G Hanley
MicroRNAs (miRNAs) are important regulators of localized mRNA translation in neuronal dendrites. The presence of RNA-induced silencing complex proteins in these compartments and the dynamic miRNA expression changes that occur in response to neuronal stimulation highlight their importance in synaptic plasticity. Previously, we demonstrated a novel interaction between the major RNA-induced silencing complex component Argounaute-2 (Ago2) and the BAR (bin/amphiphysin/rvs) domain protein PICK1. PICK1 recruits Ago2 to recycling endosomes in dendrites, where it inhibits miRNA-mediated translational repression...
June 9, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28400714/deletion-of-trpc6-attenuates-nmda-receptor-mediated-ca-2-entry-and-ca-2-induced-neurotoxicity-following-cerebral-ischemia-and-oxygen-glucose-deprivation
#19
Jin Chen, Zhaozhong Li, Jeffery T Hatcher, Qing-Hui Chen, Li Chen, Robert D Wurster, Sic L Chan, Zixi Cheng
Transient receptor potential canonical 6 (TRPC6) channels are permeable to Na(+) and Ca(2+) and are widely expressed in the brain. In this study, the role of TRPC6 was investigated following ischemia/reperfusion (I/R) and oxygen-glucose deprivation (OGD). We found that TRPC6 expression was increased in wild-type (WT) mice cortical neurons following I/R and in primary neurons with OGD, and that deletion of TRPC6 reduced the I/R-induced brain infarct in mice and the OGD- /neurotoxin-induced neuronal death. Using live-cell imaging to examine intracellular Ca(2+) levels ([Ca(2+)] i ), we found that OGD induced a significant higher increase in glutamate-evoked Ca(2+) influx compared to untreated control and such an increase was reduced by TRPC6 deletion...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28356001/atomoxetine-protects-against-nmda-receptor-mediated-hippocampal-neuronal-death-following-transient-global-cerebral-ischemia
#20
Joon Ha Park, Yang Hee Kim, Ji Hyeon Ahn, Soo Young Choi, Seongkweon Hong, Sung Koo Kim, Il Jun Kang, Young-Myeong Kim, Tae-Kyeong Lee, Moo-Ho Won, Choong-Hyun Lee
BACKGROUND: Atomoxetine has been widely used for the treatment of attention-deficit/hyperactivity disorder. ATX has additional abilities such as antagonistic effects on the N-methyl-D-aspartate receptors (NMDARs) and benefit effects in some animal models of neurological disorders. However, there were few studies regarding protective effects and related mechanisms of ATX against cerebral ischemic insults. OBJECTIVE: The objective of this study is to investigate neuroprotection of ATX pretreatment and its mechanisms in the hippocampal cornu ammonis 1 (CA1) region following transient global cerebral ischemia in gerbils...
March 27, 2017: Current Neurovascular Research
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